HealthDay News — Three antidepressents have been associated with prolonged corrected QT (QTc) interval — a marker of increased ventricular arrhythmia risk, study results show.

Two selective serotonin reuptake inhibitors, citalopram and escitalopram, and the tricyclic antidepressant amitriptyline, have been associated in a dose-related fashion with QTc interval prolongation, Roy Perlis, MD, of Massachusetts General Hospital in Boston, and colleagues reported in BMJ.

The finding does not apply to all antidepressants, the researchers noted. Other SSRIs were not associated with CTc interval prolongation, and another antidepressant, bupropion, was associated with shorter corrected QT intervals (P<0.05).

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The FDA has previously raised concerns about the risk for QT prolongation and torsades de pointes with high doses of citalopram, setting the maximum daily dose at 40 mg and contraindicating the drug in patients with congenital long QT syndrome.

But in August 2012, the agency softened the warning, replacing the contraindication with a statement that the drug was not recommended in that patient population, but that some may benefit from low doses if other alternatives are not available.

In order to better understand the relationship between antidepressant use and QT intervals, Perlis and colleagues analyzed electronic health record data from 38,397 adults (mean age 58.3) from the Partners HealthCare system, which includes Massachusetts General Hospital, Brigham and Women’s Hospital and outpatient clinics, from February 1990 to August 2011. All participants had an electrocardiogram recorded after prescription of antidepressants or methadone.

Abnormal or high QTc intervals — defined as 451 milliseconds or greater in men and 471 ms or greater in women — were observed in 20.4% of patients.

After adjusting for various potential confounding clinical and demographic variables, increasing doses of citalopram, escitalopram, and amitriptyline were associated with prolongation of QTc, whereas increasing doses of bupropion was associated with QTc shortening.

The following antidepressants were not associated with any changes in QT intervals: fluoxetine, paroxetine, sertraline, duloxetine (Cymbalta), mirtazapine, nortriptyline and venlafaxine.

When the researchers examined the effect of antidepressant dosage on QT intervals in a subset of 467 patients who had multiple electrocardiograms performed after dosage changes, they that found increasing the dose of citalopram from 10 to 20 mg daily increased the average QTc interval 7.8 ms (P<0.05). Increasing the dose from 20 to 40 mg further prolonged QTc interval by an average of 10.3-ms (P<0.01).

Conversely, increasing buproprion from 100 mg to 200 mg decreased the average QTc interval 19.2 ms (P<0.05), the researchers found.

“Our results suggest that, given its capacity to shorten QT interval, bupropion treatment might be a reasonable next step for patients partially responsive to citalopram who would otherwise require a dose increase,” the researchers noted.

Study limitations include the potential for confounding due to lack of randomization for treatment and dose, they acknowledged.


    1. Castro V et al. BMJ. 2013; doi:10.1136/bmj.f288.